AB0096 MECHANISM OF SHIP IN NEUTROPHIL EXTRACELLULAR TRAP IN RHEUMATOID ARTHRITIS
Authors: Z. Cheng, X. Tang, H. Zhang, L. Sun
Journal: Annals of the Rheumatic Diseases (2022)

Background Rheumatoid arthritis（RA） is a common autoimmune disease with unknown etiology. RA is characterized by the destruction of cartilage and bone. Neutrophils are abundant in synovial fluid of RA and are closely related to the development of RA 1 。In recent years, it has been reported that neutrophils can release neutrophil extracellular traps（NET）, which can not only kill different bacteria and viruses, but also closely related to autoimmune diseases 1,2 Studies have shown that NET is involved in the development of RA 3 . The Src homologous 2 domain containing inositol 5-phosphatase 1 (SHIP-1) controls the level of intracellular inositol 3-phosphate kinase product phosphatidylinositol-3,4,5-triphosphate. SHIP can be used as a positive or negative regulatory signal in different stimuli.And So has studied that the inflammation of CIA mouse model is reduced after SHIP is inhibited. Objectives Therefore, we want to study whether SHIP is involved in the formation of rheumatoid arthritis NET and its relationship with NET. Methods We isolated neutrophils from RA peripheral blood, stimulated NETosis with PMA, and detected the changes of NETosis in the group with SHIP inhibitor by flow cytometry and immunofluorescence. In addition, DBA mice were divided into three groups: HC, CIA and SHIP inhibitor intraperitoneal injection group. The degree of paw swelling and HE staining were used to detect the inflammation of mice, and the release of NET in CIA model was detected by flow cytometry. Results In the DBA model, the generation of neutrophil extracellular traps decreased significantly in the intraperitoneal injection group of SHIP inhibitor. SHIP inhibitor can significantly inhibit the formation of NET in RA patients. In addition, we also found TNF- α Monoclonal antibodies reduced NETosis in RA patients, while SHIP inhibitors inhibited the generation of NET in RA patients. The results suggest that SHIP may inhibit the inflammatory factor TNF- α. In turn, it is involved in the release of NET in rheumatoid arthritis Conclusion SHIP participates in the formation of NET in rheumatoid arthritis and affects the production of NET through pro-inflammatory cytokines. Therefore, SHIP is expected to become a new target for the treatment of RA. References [1]Skopelja-Gardner, S.; Jones, J. D.; Rigby, W. F. C. “NETtling” the Host: Breaking of Tolerance in Chronic Inflammation and Chronic Infection. J. Autoimmun. 2018 , 88 , 1–10. https://doi.org/10.1016/j.jaut.2017.10.008 . [2]Lee, K. H.; Kronbichler, A.; Park, D. D.-Y.; Park, Y.; Moon, H.; Kim, H.; Choi, J. H.; Choi, Y.; Shim, S.; Lyu, I. S.; Yun, B. H.; Han, Y.; Lee, D.; Lee, S. Y.; Yoo, B. H.; Lee, K. H.; Kim, T. L.; Kim, H.; Shim, J. S.; Nam, W.; So, H.; Choi, S.; Lee, S.; Shin, J. I. Neutrophil Extracellular Traps (NETs) in Autoimmune Diseases: A Comprehensive Review. Autoimmun. Rev. 2017 , 16 (11), 1160–1173. https://doi.org/10.1016/j.autrev.2017.09.012 . [3]Khandpur, R.; Carmona-Rivera, C.; Vivekanandan-Giri, A.; Gizinski, A.; Yalavarthi, S.; Knight, J. S.; Friday, S.; Li, S.; Patel, R. M.; Subramanian, V.; Thompson, P.; Chen, P.; Fox, D. A.; Pennathur, S.; Kaplan, M. J. NETs Are a Source of Citrullinated Autoantigens and Stimulate Inflammatory Responses in Rheumatoid Arthritis. Sci. Transl. Med. 2013 , 5 (178), 178ra40-178ra40. https://doi.org/10.1126/scitranslmed.3005580 . Disclosure of Interests None declared